Terfenadine antagonism against interleukin-4-modulated gene expression of T cell cytokines

Abstract

Here, we investigated whether an anti-allergy drug, terfenadine, affects interleukin-4-modulated cytokine expression in peripheral T cells. Peripheral blood T cells were first stimulated with recombinant interleukin-4 and then tested for modulation of the mRNA of a panel of cytokines using the reverse transcription-polymerase chain reaction followed by Southern blot analysis. It was found that T cells constitutively expressed mRNA specific to T helper 1 cytokines (interleukin-2, interferon-γ, tumor necrosis factor-α), which was markedly downregulated upon stimulation with interleukin-4, whereas mRNA for T helper 2 cytokines such as interleukins 4, 5, and 6 was induced in response to interleukin-4. Interestingly, the interleukin-4-induced expression of all T helper 2 cytokines examined was markedly downregulated by terfenadine. Among T helper 1 cytokines, interleukin-4-mediated suppression of tumor necrosis factor-α was not affected by terfenadine, which, however, markedly restored mRNA expression of interferon-γ or interleukin-2. Electrophoretic mobility shift assays using [32P]-labeled synthetic oligonucleotides encoding the consensus binding motif of activator protein-1 demonstrated that interleukin-4-induced binding of activator protein-1 composed of JunB was interfered by terfenadine. This study indicates that terfenadine, at least partially, interferes with interleukin-4-activated signaling, leading to terfenadine antagonism against the modulatory impact of interleukin-4 on T cell cytokines.